RecruitingPhase 2

Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression

United States50 participantsStarted 2024-11-06

Plain-language summary

Background: Major depressive disorder (MDD) is a serious mental illness that can put people at risk of self-harm and death. Many drugs are used to treat MDD, but it can take a long time for them to be effective. Researchers want to know if a faster-acting drug, (2R,6R)-hydroxynorketamine (HNK), can better treat the symptoms of MDD. Objective: To test a study drug (HNK) in people with MDD. Eligibility: People aged 18 to 70 years with MDD. They must have had a screening assessment under protocol 01-M-0254. Design: Participants will be tapered off their current MDD drugs over 2 to 5 weeks. They will stay off of the drugs for up to 2 weeks prior to starting the study medication and procedures. They will have a physical exam with blood tests. They will have tests of their heart function, mood, and thinking. They will answer questions about their symptoms. They may choose to have imaging scans and scans of their brain activity. HNK is given through a tube attached to a needle inserted into a vein. Participants will receive infusions on this schedule: They will receive 4 infusions over 2 weeks. They will stay in the clinical center overnight after each infusion or for the duration of the study. They will receive no drugs for 2 to 3 weeks. They will have 4 more infusions over 2 weeks, with overnight stays after each or for the duration of the study. One set of 4 infusions will be the HNK. The other set of 4 infusions will be a placebo. A placebo looks just like the real drug but contains no medicine. Participants will not know when they are getting the HNK or placebo. ...

Who can participate

Age range18 Years – 70 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Ability of participant to understand and willingness to sign a written informed consent document. To verify this, participants must score \>= 80% on the consent quiz.
✓. Stated willingness to comply with all study procedures and availability for the duration of the study.
✓. 18 to 70 years of age.
✓. All participants must have undergone a screening assessment under protocol 01-M-0254.
✓. Participants must fulfill DSM-IV or DSM-5 criteria for MDD, single episode or recurrent without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P). Participants must be experiencing a current major depressive episode lasting at least two weeks.
✓. Participants must have an initial score of \>= 20 on the MADRS and a YMRS score of \<12 within one week of study entry and upon entry into Phase II.
✓. Ability to take intravenous medication and be willing to adhere to the (2R,6R)-HNK regimen.
✓. Participants must have a current or past history of lack of response to at least one adequate antidepressant trial (may be from the same chemical class), with at least one in the current major depressive episode, operationally defined using the modified Antidepressant Treatment History Form (ATHF); non-response to an adequate trial of ECT or TMS would count as an adequate antidepressant trial.

What they're measuring

Change from baseline on Montgomery-Asberg Depression Rating Scale total scores

Timeframe: Baseline, Day 12

Trial details

NCT IDNCT06511908

SponsorNational Institute of Mental Health (NIMH)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2027-07-01

Contact for this trial

Solaleh Azimipour

(877) 646-3644 solaleh.azimipour@nih.gov

View on ClinicalTrials.gov More Suicide trials

Plain-language summary

Who can participate

Age range18 Years – 70 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Ability of participant to understand and willingness to sign a written informed consent document. To verify this, participants must score \>= 80% on the consent quiz.
✓. Stated willingness to comply with all study procedures and availability for the duration of the study.
✓. 18 to 70 years of age.
✓. All participants must have undergone a screening assessment under protocol 01-M-0254.
✓. Participants must fulfill DSM-IV or DSM-5 criteria for MDD, single episode or recurrent without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P). Participants must be experiencing a current major depressive episode lasting at least two weeks.
✓. Participants must have an initial score of \>= 20 on the MADRS and a YMRS score of \<12 within one week of study entry and upon entry into Phase II.
✓. Ability to take intravenous medication and be willing to adhere to the (2R,6R)-HNK regimen.
✓. Participants must have a current or past history of lack of response to at least one adequate antidepressant trial (may be from the same chemical class), with at least one in the current major depressive episode, operationally defined using the modified Antidepressant Treatment History Form (ATHF); non-response to an adequate trial of ECT or TMS would count as an adequate antidepressant trial.

Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

Contact for this trial

Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

Contact for this trial

Exclusion criteria